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ISMO Bursary Awards 2023

By Mindo - 20th Feb 2023

ISMO

The annual ISMO meeting heard presentations on a wide range of high-quality cancer research taking place in Irish hospitals

The 2023 Irish Society of Medical Oncology (ISMO) Bursary Awards took place on Friday, 27 January. It was held in the Fintan Gunne Theatre, Catherine McAuley Centre, the Mater Misericordiae University Hospital, Dublin.

The Bursary candidate presentations, which were of a high quality, focused on a wide range of subjects. This article summarises the winning presentations.

Case studies

The title of the presentation by Dr Aonghus Joyce, Cork University Hospital (CUH), was ‘Punch biopsy: A diagnostic keystone for metastatic pericardial angiosarcoma’. Angiosarcoma is a rare, aggressive malignancy originating from endothelial cells. Its diagnosis is histologically challenging. Dr Joyce’s presentation was based on a case involving multiple presentations and investigations, which were non-diagnostic until angiosarcoma was eventually diagnosed from a cutaneous lesion.

“Primary pericardial angiosarcomas are extremely rare and associated with high mortality,” according to Dr Joyce.

“Patients present with myriad symptoms depending on organ involvement. Histological diagnosis is challenging. This patient’s diagnosis was reached by punch biopsy of cutaneous lesions identified on full skin examination during his medical workup. This avoided more invasive procedures for tissue diagnosis, which had been planned.”

Dr Harriet Byrne, CUH, made a presentation titled ‘No MRONJ, no problem?’. Medication-related osteonecrosis of the jaw (MRONJ) is a clinical risk for patients on bisphosphonate therapy. The use of polypharmacy and variable regimes of antiresorptives, antiangiogenics, and immunotherapies for cancer implies an undisputable risk of MRONJ when prescribed as a targeted, or combination, therapy. The burden of dental disease, an initiating factor of MRONJ, has remained stagnant and increasingly relevant to the bone modifying agent prescriber. Reduced globalised awareness of dental disease and poor progress to combat dental disease was highlighted by the recent World Health Assembly Global Resolution 74.5 (May 2021). In this presentation, Dr Byrne illustrated a case of MRONJ, following administration of bisphosphonates for metastatic breast cancer.

“This case highlights the relevance of dental care in the setting of oncology patients on antiresorptive therapy,” according to Dr Byrne.

“The risk of MRONJ remains, even years after active bisphosphonate therapy. In the absence of proactive dental oncology protocols, we anticipate that in the coming decades, MRONJ will become increasingly relevant. The literature to date has reached no definitive consensus about the treatment and management of MRONJ, which heightens the importance of the role of preventative care for these patients. Antiresorptives have progressed from oncological regimes in the palliative setting to curative disease. This results in another cohort of patients exposed to bisphosphonates and at risk of MRONJ. For the practicing oncologist today, MRONJ risk is relevant.”

‘Primary STK11 adnexal tumour: A challenging diagnosis’ was the title of the presentation by Dr Róisín Rynne, CUH.

Primary STK11 adnexal tumours are a novel entity of rare malignancies harbouring a serine/threonine kinase 11 (STK11) gene mutation, which was first described in August 2021. STK11 encodes the protein liver kinase B1 (Lkb1). This protein plays key roles in cellular metabolism, cell polarity and DNA repair. Germline mutations in this gene leads to Peutz-Jeghers Syndrome (PJS), an autosomal dominant syndrome characterised by hamartomatous polyposis, mucocutaneous pigmentation, and a lifetime risk of cancer ranging from 37 to 93 per cent. Dr Rynne discussed the experience with the challenges of diagnosis and management of this unique and newly defined tumour, with reference to a case study.

“There are currently 23 cases of primary STK11 adnexal tumours described in the literature, with 50 per cent of these cases being associated with PJS,” according to Dr Rynne.

“This histologically diverse tumour with a variable immunohistochemical profile is currently poorly understood and it is likely that it was previously mislabelled as female adnexal tumours of Wolffian origin and endometroid carcinomas. The comprehension of its features and natural history will become clearer as new cases are reported. It is anticipated to be an aggressive tumour with 50 per cent having metastases at diagnosis and an 80 per cent recurrence rate reported as part of the original case series published in 2021. However, further research is required to truly establish the prognostic signature of this tumour.”

The burden of dental disease, an initiating factor of MRONJ, has remained stagnant and increasingly relevant to the bone modifying agent prescriber

Data

A study presented by Dr Rachel Clarke, University Hospital Waterford (UHW), examined the effect of excess weight on outcomes and immune-related adverse events following pembrolizumab treatment. A single-centre, retrospective audit of all patients who received pembrolizumab treatment between July 2019 to July 2022 was conducted. The primary aim was to assess the effect of obesity on clinical outcome and immune-related adverse events (IrAEs).

A total 70 patients who had received pembrolizumab in UHW were identified during the period studied. Of these, 31 patients did not have sufficient data to document BMI in outpatient records or in the pharmacy database and therefore were excluded. Out of the 39 patients analysed, 19 (47.5 per cent) were male and 11 patients (27.5 per cent) included were obese (BMI >30). The median age of patients included was 65 years [60-72] and median BMI was 28 [16-40.4]. Objective radiological response (ORR) was achieved in 11 patients (28 per cent), the median progression-free survival (PFS) was five months [one-45 months] and overall survival (OS) was 12 months [two-54 months].

The PFS was not significantly higher in patients with BMI >30 (five months vs four months, p=0.49), nor was OS (nine months vs 12 months, p=0.587). The objective response rate was not significantly higher in the obese group (63.6 per cent vs 75 per cent, p=0.47). The incidence of IrAEs was not significantly increased in patients with BMI >30 (33.3 per cent vs 22.2 per cent, p=0.46). The most common IrAEs in the study population were endocrinopathies, rash, and colitis.

“While this study does not reveal any differences in the outcomes and IrAEs comparing obese patients versus non-obese patients, this may be due to the small sample size,” according to Dr Clarke. “However, it does highlight the need for further research into the area as understanding this process may improve clinical outcomes for patients.”

The presentation by Dr Shane O’Sullivan, Mater Private Hospital, Dublin, concerned the use of ovarian function suppression (OFS) in combination with endocrine therapy in premenopausal women with breast cancer (BC).

Long-term follow-up of clinical trials studying the addition of OFS to adjuvant endocrine therapy have shown sustained improvements in disease free survival and recently for the first time an improvement in OS for premenopausal women with hormone receptor-positive BC.

There are no standard recommendations by professional societies regarding the optimal choice of gonadotropin releasing hormone (GnRH) analogue, or dose and frequency of administration. Practice guidelines also do not provide recommendations on how patients receiving OFS should be monitored.

A survey was designed to determine how medical oncologists manage and monitor OFS in premenopausal women. 

Most oncologists (70 per cent) reported using goserelin; 10 per cent triptorelin and 20 per cent leuprorelin.  GnRH analogues were given monthly by 60 per cent; three-monthly by 14 per cent and others stated age, tolerance, and receipt of chemotherapy influenced their decision. There was significant variation in how GnRH analogues were initiated. One-third performed routine hormone profiles others reported sometimes (64 per cent) or never (five per cent). All testing was performed in local laboratories.

“OFS is considered standard of care for high-risk premenopausal women with ER-positive BC,” according to the study’s conclusion.

“Our study shows how we administer and monitor it varies among specialists. We are expanding our survey internationally through ASCO [American Society of Clinical Oncology] and will open a study to understand the prevalence of ovarian function escape during OFS.”

The presentation by Ms Shivika Marwaha, CUH, was based on an assessment of real-world outcome of durvalumab in non-small cell lung cancer (NSCLC) post completion of concurrent  chemoradiotherapy. Consolidative durvalumab is recommended as per PACIFIC clinical trial with significant benefit in median PFS of 16.8 months as compared to placebo.

A retrospective analysis of patients with NSCLC who received consolidative durvalumab from January 2021 to January 2023 was carried out. Clinicopathological data was collected. The duration of treatment and need for drug discontinuation, in addition to treatment related adverse events, recurrence free, and overall survival of patients was gathered.

“Our real-world analysis in our ongoing study with 14 patients to date has shown a median duration of treatment of seven months, high rate of treatment-related adverse events and median progression free survival of 10 months,” according to Ms Marwaha.

“Careful discussions of benefits of durvalumab and risks of toxicity are needed.”

Dr Catherine Weadick, CUH, spoke about risk stratification tools to help decide on adjuvant chemotherapy usage in resected soft tissue sarcomas (STS).

All new patients with resected soft tissues sarcoma discussed in the STS multi-disciplinary team’s meeting in CUH between Jan 2017 – Dec 2021 were identified. The histology and imaging of the identified patients were reviewed. Data regarding demographics, histology, treatment, and outcomes was collected. Risk assessment was done on all patients with an extremity or trunk sarcoma.

A total 93 patients were identified as having an STS resected – 61 of these were located on the trunk or extremities. This represented 24 different histological subtypes. Sarculator score was calculated for 41 of these patients (well differentiated liposarcomas and dermatofibrosarcoma protuberans were excluded). Two patients received adjuvant chemotherapy and one patient neoadjuvant chemotherapy.

“Our cohort is representative of the broad histological subtypes expected in sarcoma,” according to the conclusion.

“Sarculator score results correlate with international outcomes, with higher scores associated with increased mortality.  In our cohort, sarculator score was more predictive of outcome than tumour grade/size.”

The title of the presentation by Dr Darragh O’Sullivan, UHW, was ‘The prevalence of statin use in geriatric oncology. Is there a role for cessation?’. Dr O’Sullivan said there is a need for clarity on the role of statins in geriatric oncology and when to de-prescribe. Data was retrospectively collected from a prospectively maintained database of patients attending the geriatric oncology assessment and liaision (GOAL) clinic in the South East Cancer Centre, UHW, since 2017.

“Overall survival of patients within this clinic is short of the 2.5 years required to provide benefit, based on meta-analysis results,” according to the conclusion.

“Therefore, there is evidence to stop this medication in the primary preventative group, once diagnosed with advanced cancer. The stage 4 disease group included patients undergoing secondary prevention, so treatment is, therefore, more efficacious. However, with an overall survival of 1.44 years, the window for benefit is small. A guideline would be helpful to guide clinical decision-making in this setting.”

The study presented by Dr Ronan McLaughlin, St Vincent’s University Hospital, Dublin, was on a real-world analysis of the clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage node positive breast cancer in Ireland.

The study looked at clinical and economic impact of RS testing on treatment decisions in node positive patients. From November 2011 to October 2022, a retrospective, cross-sectional observational study was performed of HR+, 1-3 node positive (N+) patients who had RS testing across two of Ireland’s largest oncology centres.

“Ireland was one of the first public healthcare systems to approve reimbursement for RS testing in N+ pts,” according to the conclusion.

“Over the period of this study a 55 per cent reduction in CT use was achieved with savings of over €1 million.”

Dr Aislinn Reilly, Beaumont Hospital, Dublin, presented on a study that examined biomarkers of response to immunotherapy in advanced NSCLC. Dynamic changes in cell-free DNA (cfDNA) or circulating tumour DNA (ctDNA) may represent a biomarker of response to immune checkpoint inhibitor-based therapy (ICI) in NSCLC. The study sought to explore the hypothesis that molecular response (MR) in cfDNA detected in exhaled breath condensate (EBC) and/or blood is associated with radiographic response to ICI+/-chemotherapy (RR).

A total of 10 patients were identified and provided pre- and on-treatment EBC and blood samples.

“In this descriptive analysis, we identify that dynamic changes occur in cfDNA in the EBC and blood in patients with NSCLC treated with ICI+/-chemotherapy,” according to the study’s conclusion.

“Specifically, we identify that a subset of patients with radiographic response to treatment have a MR in EBC+/-blood. Based on this, a prospective study is underway to evaluate MR in EBC+blood as a biomarker of response to ICI+/-chemotherapy in aNSCLC (n=108).”

Genomics

Dr Karine Ronan, UHW, spoke about a multi-centre study, frequency of next-generation sequencing (NGS), prevalence of targetable mutations and response to targeted therapies among patients with metastatic urothelial cancer (mUC) in Ireland.

The study assessed the frequency of NGS, using either Oncomine or Foundation One panels in mUC patients at a number of cancer centres in Ireland, to ascertain the prevalence of genomic alterations in this population.

A total of 111 patients diagnosed with mUC between 2017 and 2022 were identified for inclusion.

“Our findings support the evidence that mUC is associated with a high prevalence of genetic alterations, which contributes to the therapeutic challenge of identifying actionable driver mutations amenable to targeted therapy,” according to the study.

“Observed responses to targeted therapies provide information to guide future investigation and clinical trial development.

“Although not all drugs with efficacy against targetable mutations are available in Ireland, identifying these mutations by carrying out NGS may define patient eligibility for clinical trials and is important.

“We observed a high prevalence of FGFR alterations, in line with published rates. The prevalence of ERBB2 alterations was lower in our study compared with published data. This may be related to the majority of NGS tests being carried out on initial tumour specimens, while a higher prevalence of ERBB2 mutations has been observed in metastatic lymph node biopsies.

“Response rates to trastuzumab combined with chemotherapy observed in this study were overall poor.  Although the prevalence of ERBB2 mutations in mUC is higher than most other malignancies, further research is required to improve therapeutic responses to HER2-directed therapies.”

‘The genomic landscape of non-small cell lung cancer in the Republic of Ireland,’ was the title of the presentation by Dr Rachel Keogh, CUH.

The study aimed to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumours harbour actionable genomic alterations via broad NGS panel testing (eg, EGFR, ALK, KRAS, NRAS, BRAF, KIT, ROS1, RET, MET amplification, METexon14 skipping, PDGFRA, NTRK, HER2, FGFR).

A total of 2,249 patients were included.

Actionable alterations were identified in 52.6 per cent of patients. KRAS was the most common oncogenic driver identified, of which KRAS G12C was most frequent. The study revealed a lower prevalence of patients with EGFR mutations and either ALK, ROS1, and RET fusions compared to similar datasets.

“These data have important implications for treatment prioritisation and clinical trial selection in the Republic of Ireland,” according to Dr Keogh.

Dr Mairi Lucas, St Vincent’s University Hospital, Dublin, presented on a study looking at tumour infiltrating lymphocytes (TILs) in hormone positive/HER 2 negative breast cancer. Archival tissue samples from patients in Ireland with early-stage ER+/HER2- breast cancer were used. A total of 409 samples were included in the analysis.

“The role of TILs in ER+/HER2 breast cancer is still undefined,” according to the study.

“While the majority of ER+/HER2 breast cancer samples had low numbers of TILs, there is clear heterogeneity within this subgroup. Further research is needed to assess how TILs may influence treatment response and prognosis.”

Phase III SUNLIGHT trial achieved ‘clinically meaningful improvement’ in overall survival

Data from SUNLIGHT, shared at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco last month, showed the phase III trial met its primary endpoint of overall survival (OS).

The SUNLIGHT trial investigated the efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone in patients with refractory metastatic colorectal cancer (mCRC) following disease progression or intolerance on two prior chemotherapy regimens. Results from the main analysis demonstrated that the investigational combination provided a statistically significant and a clinically meaningful improvement in OS of 3.3 months compared to trifluridine/tipiracil alone (10.8 months vs 7.5 months, hazard ratio [HR]: 0.61, 95 per cent confidence interval [CI]: 0.49-0.77, p<0.001). This improvement in OS represents a 39 per cent reduction in the risk of death in patients with refractory mCRC.

Regarding the key secondary endpoint, there was a statistically significant improvement for the trifluridine/tipiracil plus bevacizumab combination versus trifluridine/tipiracil alone in progression-free survival (5.6 months vs 2.4 months, HR: 0.44, 95 per cent CI: 0.36-0.54, p<0.001).

“The prognosis for metastatic colorectal cancer patients who do not respond to chemotherapy remains poor, with median survival times typically ranging from four-to-eight months,” said Prof Josep Tabernero, Head of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, and Principal Investigator for the SUNLIGHT trial.

“Coupled with the fact that cases of colorectal cancer are increasing, there is an urgent need for new treatment options that can extend survival in patients with metastatic colorectal cancer in the later stages of disease. Findings from the SUNLIGHT trial represent an important development, which will be welcomed by the colorectal cancer community.”

Observed responses to targeted therapies provide information to guide future investigation and clinical trial development

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